Induction Chemotherapy Using Cyclophosphamide and Topotecan in Treating Patients Who Are Undergoing Autologous Peripheral Stem Cell Transplantation for Newly Diagnosed or Progressive Neuroblastoma

Overview

RATIONALE: Drugs used in chemotherapy, such as topotecan and cyclophosphamide, use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of induction chemotherapy using cyclophosphamide and topotecan in treating patients who are undergoing surgery and autologous stem cell transplantation followed by radiation therapy for newly diagnosed or progressive neuroblastoma.

OBJECTIVES: Primary * Determine the toxicity and feasibility of adding cyclophosphamide and topotecan to induction therapy in patients with newly diagnosed or progressive high-risk neuroblastoma undergoing autologous peripheral blood stem cell (PBSC) transplantation. * Determine the feasibility of PBSC mobilization and in vivo PBSC tumor purging in these patients after treatment with this regimen. Secondary * Determine tumor response rate in patients treated with this regimen. * Determine the pharmacokinetics of this regimen in these patients. * Determine whether topotecan affects cyclophosphamide pharmacokinetics in these patients. * Correlate host DNA with toxicity and cyclophosphamide and topotecan pharmacokinetics in patients treated with this regimen. * Determine toxicity in patients treated with this regimen. OUTLINE: This is a pilot, multicenter study. Patients are stratified according to diagnosis (newly diagnosed vs initially stage 1, 2, or 4S that progressed to stage 4 without interval chemotherapy). * Induction therapy: Patients receive 6 courses of induction therapy. * Courses 1 and 2: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 6 and continuing until blood counts recover. * Course 3: Patients receive etoposide IV over 2 hours on days 1-3, cisplatin IV over 1 hour on days 1-4, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. * Course 4: Patients receive cyclophosphamide IV over 6 hours on day 1 and doxorubicin IV and vincristine IV continuously over 24 hours on days 1-3. Patients also receive G-CSF SC or IV beginning on day 4 and continuing until blood counts recover. * Course 5: Patients receive etoposide, cisplatin, and G-CSF as in course 3. * Course 6: Patients receive cyclophosphamide, doxorubicin, vincristine, and G-CSF as in course 4. Treatment repeats every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. * Consolidation therapy: Within 4-6 weeks after completing induction therapy, patients receive melphalan IV on days -7 to -5 and etoposide IV and carboplatin IV continuously over 24 hours on days -7 to -4. * Stem cell transplantation: Peripheral blood stem cells are collected after course 2 of induction therapy and infused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. * Surgery: After course 5 of induction therapy, patients undergo surgery. * Radiotherapy: Beginning 28-42 days after transplantation, patients receive 12 fractions of local radiotherapy to all areas of residual soft tissue disease and the primary tumor site, even if completely resected. * Maintenance therapy: Beginning 66 days after transplantation, patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 10-29 patients will be accrued for this study within 2 years.